1. Field of the Invention
Hepatocellular carcinoma (liver cancer) is a very common form of cancer. Detection of hepatocellular carcinoma is problematic, often resulting in late diagnosis. Late diagnosis, in turn, can render treatment ineffective due to the advanced state of the disease and the extent of liver involvement.
A blood test capable of sensitive and accurate detection of hepatocellular carcinoma would be most useful. Such a test could be used to screen patients for early detection of the cancer at a stage where it could still be treated. The test could also be used with patients undergoing treatment to continuously monitor the status of the disease.
At present, the best serological test for hepatocellular carcinoma is the measurement of .alpha.-fetoprotein. While this test is widely used and has proved to be a highly useful tool in cancer detection, it suffers from certain drawbacks. Elevated serum .alpha.-fetoprotein levels do not occur much earlier than other clinical symptoms, and not all liver tumors result in such increases in .alpha.-fetoprotein. Moreover, elevated .alpha.-fetoprotein titers are present in normal individuals, most notably being associated with infancy, pregnancy and periods of liver regeneration. Thus, an .alpha.-fetroprotein assay is at best equivocal and is entirely unsuitable for patients who are pregnant, who are infants, or who have undergone liver surgery. The latter class includes individuals who have undergone surgery for the removal of liver tumors where it would be of great benefit to monitor for possible recurrence.
Thus, it is desirable to provide for the detection in serum of an alternate tumor antigen or tumor marker which can be related to the presence of liver cancer. In particular, it would be desirable to provide a serum assay capable of detecting preneoplastic conditions in the liver.
2. Description of the Prior Art
Farber and his co-workers identified a soluble protein associated with hepatic preneoplastic lesions in rats. This protein was called preneoplastic antigen (PNA). See, Farber (1973) Methods in Cancer Research VII, page 345; Okita et al. (1974) Cancer Research 34:2758; Okita and Farber (1975) Gann Monograph on Cancer Research 17:283-299; and Okita et al. (1975) J. Natl. Cancer Inst. 54:199-202. PNA was shown to be microsomal epoxide hydrolase by Levin et al. (1978) Proc. Natl. Acad. Sci. USA 75:3240-3243. Levin et al. failed to detect microsomal epoxide hydrolase activity in the serum of rats suffering from hepatocellular carcinoma. Microsomal epoxide hydrolase activity in the cytosol of rat liver cells has been shown to be induced following exposure to certain carcinogens and to be at very high levels in hepatic neoplastic nodules. Novikoff et al. (1979) Proc. Natl. Acad. Sci. USA 76:5207. An enzyme-linked immunosorbent assay for the detection of microsomal epoxide hydrolase was used to detect the hydrolase in rat microsomal proteins and rat liver cytosol. Gill et al. ( 1982) Carcinogenesis 3:1307-1310.